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Biomedical subjects

K Takagi

Publications and source records attributed to K Takagi.

At least 163 records · Page 9Linked to original sources

How should a subarachnoid hemorrhage grading scale be determined? A combinatorial approach based solely on the Glasgow Coma Scale.

OBJECT: The purpose of this study was to present a combinatorial approach used to develop a subarachnoid hemorrhage (SAH) grading scale based on the patient's preoperative Glasgow Coma Scale (GCS) score. METHODS: There are 4094 different combinations that can be used to compress the 13 scores of the GCS into two to 12 grades. Break points, the positions in the scale in which two adjacent scores connote a significantly different outcome, are obtained by a direct comparison of the GCS and the Glasgow Outcome Scale (GOS). Guided by the break points, the number of combinations to be considered can be limited. All possible combinations are statistically analyzed with respect to intergrade differences in outcome. Single combinations, with the maximum number of grades having maximum intergrade outcome differences for each corresponding set of adjacent grades, must be selected. The authors verified the validity of this combinatorial approach by retrospectively analyzing 1398 consecutive patients with aneurysmal SAH who underwent surgery within 7 days of the last hemorrhage episode. The patients' GCS scores were assessed just before surgery and their GOS scores were estimated 6 months post-SAH. The combinatorial approach yields only one acceptable grading scale: I (GCS Score 15); II (GCS Scores 11-14); III (GCS Scores 8-10); IV (GCS Scores 4-7); and V (GCS Score 3). CONCLUSIONS: The combinatorial approach, guided by the break points, is so simple and systematic that it can be used again in the future when revision of the grading scale becomes necessary after development of new and effective treatment modalities that improve patients' overall outcome.

Age Factors↗

[Treatments for post-pneumonectomy pyothorax without broncho-pleural fistula: irrigation of the post-pneumonectomy space].

Between January 1986 and December 1997 pneumonectomy was performed in 58 patients. Of the 58 patients, four had pyothorax without broncho-pleural fistula. Four patients underwent chest tube drainage and irrigation of the post-pneumonectomy space, and one of which died of lung cancer during treatment for pyothorax. Two had no evidence of recurrent infection, and one had a chest wall fistula after about one year and a fistulectomy was performed. These observations suggest that draining and irrigating of the post-pneumonectomy space are effective and non-invasive methods for treating post-pneumonectomy pyothorax without broncho-pleural fistula. However we were not able to investigate specific methods, fluid types, or irrigation time frames.

Empyema, Pleural↗

[The prevalence of TTV infection and the route of TTV transmission in hemodialysis patients--compared with HCV infection].

Recently a novel virus named TT virus (TTV), associated with posttransfusion hepatitis, was isolated. The prevalence of TTV infection and the route of TTV transmission in HD units was investigated. TTV was detected in 51.3% of patients on HD (59/115), as compared with 16.5% of healthy blood donors (15/91). The prevalence rate of TTV in the patients without history of blood transfusion was similarly high (51.6%), compared with that of those with history of blood transfusion (51.2%). The prevalence rate of TTV did not differ according to the duration of HD. These suggest that the risk of TTV infection is very high in HD units and there is another major route of TTV transmission than blood transfusion.

Biomarkers↗

Effects of bacterial endotoxin on drug pharmacokinetics.

Bacterial endotoxin (lipopolysaccharide) has a variety of biological and immunological activities. Endotoxin-induced physiological changes in several organs might modify the pharmacokinetic behavior, including the biliary and urinary excretions and hepatic metabolism, of various drugs. We have conducted a series of studies as part of a program for the development of guidelines for the safe use of various drugs in patients with Gram-negative bacterial infections. We have found that endotoxin isolated from Klebsiella pneumoniae dramatically reduces renal and biliary excretion of organic anionic drugs actively secreted into the urine and bile, respectively. More recently, we found that K. pneumoniae endotoxin decreases the activity of cytochrome P450-mediated drug-metabolizing enzymes in a time-dependent manner. This article reviews recent progress in the description of pharmacokinetic properties of drugs during conditions of endotoxemia, focusing especially upon the effects of K. pneumoniae endotoxin on the hepatic metabolism and biliary excretion of drugs, and the relationship between pharmacokinetic changes and various endotoxin-induced mediators.

Animals↗

[Design and development of one-handed denture brush for bedridden people].

Oral care for elderly bedridden people is one of the most necessary forms of care, not only for prevention of oral infection or aspiration pneumonia, but also in order to savor the taste of food and to recover and maintain mental vitality through the improvement in oral function. We designed denture brush that can be handled with one-hand in order to support independence. People require cooperation between medical treatment, health, and welfare services. We introduced the newly designed denture brush as a means to support the improvement of QOL for elderly bedridden people, and we hope to see the spread and promotion of oral care.

Activities of Daily Living↗

Assessment of coronary artery bypass surgery by exercise thallium imaging.

The purpose of this study was to assess the coronary artery bypass grafting (CABG) in exercise thallium-201 scintigraphy. The study was performed on 18 consecutive patients undergoing elective surgery. We compared the results of the scintigraphic examinations, 1 week before and 1 month postoperatively. Of the 47 bypass grafts, 20 (42. 6%) grafts contributed to the improvement of the ischemic areas and 38% of the bypass grafts did not change the scintigraphic patterns after surgery. Some bypass grafts had been performed on the stenotic arteries that dominated the areas which preoperatively showed normal exercise scintigraphic patterns yet were considered to worsen in the near future. Such grafts main contribution may be to protect and to increase the overall myocardial washout ratio for prevention of an enlargement of ischemic areas.

Aged↗

A method for the measurement of glucose oxidation using the constant infusion of stable isotope.

We developed a method to measure the oxidation of glucose using the primed constant infusion of [U-13C] glucose in critically ill patients fed by total parenteral nutrition. The results obtained from the isotopic method were compared to those from indirect calorimetry in the critically ill patients. A patient with esophageal carcinoma was used for the preliminary study. The study was performed on the third postoperative day, assuming severely stressed state. Priming doses of NaH13CO3 at a dosage of 0.32 mg/kg and D-[U-13C] glucose at a dosage of 0.32 mg/kg were injected. D-[U-13C] glucose was then infused at an infusion rate of 0.004 mg/kg/min. It was revealed that the time required for an isotopic plateau was approximately 45 min in plasma glucose and 120 min in an expired air in highly stressed state. Isotopic measurement and indirect calorimetry were performed simultaneously pre- and postoperatively on three patients who underwent surgery for esophageal carcinoma. Increased fat oxidation was obtained by the isotopic method, whereas indirect calorimetry indicated nonprotein RQ above 1.0. Isotopic measurement offered a useful information that cannot be obtained from indirect calorimetry concerning the energy metabolism in the critical illness. Thus our method for the measurement of glucose oxidation is both simple and useful in investigating the energy metabolism in critically ill patients.

Blood Glucose↗

Alteration by maternal pinealectomy of fetal and neonatal melatonin and dopamine D1 receptor binding in the suprachiasmatic nuclei.

The effects of maternal melatonin on fetal and neonatal melatonin and dopamine D1 receptor systems in the central nervous system, mainly in the suprachiasmatic nuclei (SCN), were investigated after pinealectomy of rats at day 7 of pregnancy. 125I-labelled iodomelatonin injected intravenously into the pregnant rats (at day 21) was transferred in considerable amount into the fetal circulation. In vitro autoradiography data demonstrated an increase in the melatonin binding activity in the fetal (embryonic day 21) and early postnatal SCN (postnatal day 3) caused by maternal pinealectomy. This upregulation of the melatonin receptor in the SCN was then normalized after the melatonin system of the neonate started to work. The pregnant rats themselves did not show such a change in their melatonin receptors in the SCN following pinealectomy. Dopamine D1 receptor binding was affected by pinealectomy exclusively in the SCN of fetal and neonatal rats as well as in that of mothers. These results clearly indicate that the fetal circadian clock in the SCN is controlled and prepared before birth to some extent by maternal melatonin rhythm.

Animals↗

Activation of protein kinase C alpha enhances human growth hormone-binding protein release.

The effect of phorbol ester on human growth hormone-binding protein (hGH-BP) release was investigated. The hGH-BP release from human IM-9 cells measured by immunoblotting was dose-dependently enhanced by a phorbol ester, phorbol 12, 13-dibutyrate (PDBu), and reached plateau at 100 nM. The increased hGH-BP release was shown after 10 min incubation with PDBu and reached a plateau at 60 min after stimulation. Similarly, a diacylglycerol analogue, 1-oleoyl-2-acetyl-sn-glycerol, enhanced hGH-BP release. The enhancement was not inhibited by cycloheximide pretreatment, suggesting that the enhanced hGH-BP release does not require de novo protein synthesis. The PDBu-enhanced hGH-BP release was strongly inhibited by extracellular EDTA, and was dose-dependently inhibited by protein kinase C (PKC)-specific inhibitor, Ro 31-8220. These results suggest that activation of PKC mediates the PDBu-enhanced hGH-BP release. Of the 11 known PKC isoforms in human cells, PKCalpha, delta, mu and iota were detected in IM-9 cells by immunoblotting. Of these isoforms, PKCalpha, delta and mu were present in the membrane fraction, which is a known activation marker of PKC. Furthermore, when several PKC-specific inhibitors (Gö 6976, GF 109203X or bisindolylmaleimide III) with different specificities for each isoform were used, there was a good correlation between inhibition of the enhancement of hGH-BP release and inhibition of the phosphorylation of PKC isoforms, another activation marker of PKC, in PKCalpha but not in PKCdelta and mu. These results suggest that activation of PKCalpha is involved in PDBu-enhanced hGH-BP release.

Carrier Proteins↗

Induction of apoptosis by Smad3 and down-regulation of Smad3 expression in response to TGF-beta in human normal lung epithelial cells.

Smad family members are essential intracellular signaling components of the transforming growth factor-beta (TGF-beta) superfamily involved in a range of biological activities. Two highly homologous molecules, Smad2 and Smad3, have so far been identified as receptor-activated Smads for TGF-beta signaling and have become the focus of intensive studies. However, no definite differences in regulation or function have been established between these TGF-beta signaling molecules. In the present study, we show that the expression of Smad3, but not its close relative, Smad2, is down-regulated by TGF-beta mediated signals themselves in human lung epithelial cells. This down-regulation of Smad3 by TGF-beta treatment did not appear to result from shortening of the half-life of Smad3 mRNA. Constitutive expression of Smad3 in the presence of TGF-beta induced apoptotic cell death, with an adverse effect on the cell growth of human lung epithelial cells. Apoptotic cell death could also be induced by forced expression of Smad2 in the presence of TGF-beta, but less efficiently than by that of Smad3. These findings clearly define the distinctions between Smad2 and Smad3 for the first time in that a qualitative difference was observed with regard to the regulation of their expression in response to TGF-beta, while Smad2 and Smad3 appeared to have quantitatively different capabilities regarding the induction of apoptotic cell death in human lung epithelial cells.

Apoptosis↗

Monocyte chemoattractant protein-1 in the intervertebral disc. A histologic experimental model.

STUDY DESIGN: Monocyte chemoattractant protein-1 was investigated in an experimental rat model using immunohistochemistry. OBJECTIVE: To ascertain the precise mechanism of macrophage recruitment in the early phase of disc resorption. SUMMARY OF BACKGROUND DATA: In previous studies, many investigators reported that disc herniation was resorbed by monocytic phagocytosis. However, how the recruitment of monocytes was triggered is still unknown. METHODS: The autologous intervertebral discs from tails of Wistar rats were subcutaneously implanted into the abdomen. These discs were obtained on days 2, 3, 7, and 14 after implantation and were used for immunohistochemical study and for quantitative analysis of monocyte chemoattractant protein-1 by sandwich enzyme-linked immunosorbent assay. RESULTS: Monocyte chemoattractant protein-1-positive granulocytes and macrophages were observed surrounding the intervertebral disc, and monocyte chemoattractant protein-1-positive disc chondrocytes were observed in the nucleus pulposus and the inner anulus fibrosus on day 3. By day 7, monocyte chemoattractant protein-1-positive and TRPM-3-positive macrophages appeared in the granulation tissue, and some of these cells invaded the nucleus pulposus and inner anulus fibrosus. The concentration of monocyte chemoattractant protein-1 was highest on day 3. CONCLUSION: Intervertebral disc chondrocytes have chemotactic properties and play an active role in the recruitment of monocytes involved in disc resorption.

Animals↗

Cloning and characterization of the cDNA for human airway trypsin-like protease.

Previously we isolated a trypsin-like enzyme designated human airway trypsin-like protease from the sputum of patients with chronic airway diseases. This paper describes the cDNA cloning, characterization of the primary protein structure deduced from the cDNA, and gene expression of this enzyme in various human tissues. We obtained an entire 1517-base pair sequence of cDNA with an open reading frame encoding a polypeptide with 418-amino acid residues. The polypeptide consisted of a 232-residue catalytic region and a 186-residue noncatalytic region with a hydrophobic putative transmembrane domain near the NH2 terminus. The polypeptide was suggested to be a type II integral membrane protein in which the COOH-terminal catalytic region is extracellular. Therefore, this protein is thought to be synthesized as a membrane-bound precursor and to mature to a soluble and active protease by limited proteolysis. It showed 29-38% identity in the sequence of the catalytic region with human hepsin, enteropeptidase, acrosin, and mast cell tryptase. The noncatalytic region had little similarity to other known proteins. In Northern blot analysis a transcript of 1.9 kilobases was detectable most prominently in the trachea among 17 human tissues examined.

Amino Acid Sequence↗

Compared effects of natriuretic peptides on ovalbumin-induced asthmatic model.

We compared the effects of natriuretic peptides on antigen-induced bronchoconstriction and airway microvascular leakage in sensitized guinea pigs. Anesthetized male guinea pigs, ventilated via a tracheal cannula, were placed in a plethysmograph to measure pulmonary mechanics for 10 min after challenge with 1 mg/kg of ovalbumin, and then Evans blue dye was extravasated into airway tissue in order to indicate and evaluate microvascular leakage. Three separate intravenous pretreatments using atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) significantly inhibited the ovalbumin-induced bronchoconstriction and microvascular leakage in a dose-dependent manner. These inhibitory effects were mimicked by 8-bromoguanosine 3',5'-cyclic monophosphate. We showed that the rank order of inhibitory potencies, which were mediated by cyclic guanosine 3',5'-monophosphate, was BNP > or = ANP > or = CNP. These results gave us some clues for the clinical application of the natriuretic peptides.

Animals↗

Analysis of the murine Hoxa-9 cDNA: an alternatively spliced transcript encodes a truncated protein lacking the homeodomain.

Hoxa-9 is one of the homeo box (Hox) genes exhibiting similarity to the Drosophila Abdominal B gene. So far, only partial nucleotide sequences have been reported for mouse Hoxa-9 cDNA (Rubin et al., (1987) Mol. Cell. Biol. 7, 3836-3841). Here, we have determined the nucleotide sequence of the 5'-region of mouse Hoxa-9 cDNA and its genomic structure. Mouse Hoxa-9 cDNA contains a complete ORF encoding a protein of 271aa exhibiting 96.7% identity to its human counterpart. Interestingly, an alternatively spliced transcript (Hoxa-9T) was identified by RT-PCR. Sequence analysis revealed that 173bp within the Hoxa-9 ORF was missing from the Hoxa-9T cDNA. This additional splicing would potentially result in a frameshift, leading to the production of a truncated protein lacking the homeobox. Northern blot analysis revealed that the probe containing the homeodomain hybridized to two major transcripts (2.5 and 1.9kb) in the trunk region of 12.5 dpc embryos, and adult kidney and large intestine. On the other hand, the probe containing the additional intron detected only 2.5kb transcript in the same tissues, indicating that 1.9kb transcript corresponds to Hoxa-9T mRNA. We have also determined the transcriptional start site of Hoxa-9T.

Alternative Splicing↗

Molecular cloning of human TAK1 and its mutational analysis in human lung cancer.

In previous reports, we described that DPC4/Smad4 and Smad2 are mutated in a fraction of human lung cancers and suggested possible roles of the downstream mediators of transforming growth factor-beta (TGF-beta)-elicited signals in the pathogenesis of this most common cancer. In the present study, we investigated whether another downstream mediator, human TGF-beta-activated kinase 1 (hTAK1), also is altered in lung cancer. For this purpose, the hTAK1 gene was cloned with the aid of an expression sequence tag database search and cDNA library screening, and hTAK1 was found to be expressed ubiquitously in 2 distinct isoforms regulated in a tissue-specific manner in fetal and adult normal tissues. Interestingly, hTAK1 was assigned to the chromosome region 6q14-21, which is deleted frequently in various human malignancies, including lung cancer. Despite our extensive search for alterations in 39 lung cancer specimens as well as in 16 lung cancer cell lines, somatic mutations of hTAK1 were not identified, indicating that hTAK1 itself is not a frequent target for genetic alterations in lung cancer.

Amino Acid Sequence↗

IL-8 is an essential mediator of the increased delayed-phase vascular permeability in LPS-induced rabbit pleurisy.

We investigated the involvement of IL-8 in the delayed vascular permeability (VP) in rabbit lipopolysaccharide (LPS)-pleurisy. Maximal level of interleukin-8 (IL-8) was detected in pleural fluid at 2 h after LPS injection and anti-IL-8 inhibited the delayed VP by 90%. Injection of homologous IL-8 induced VP, the time-course of which preceded that of LPS-induced delayed VP. Production of IL-8 in LPS-pleurisy was inhibited with anti-tumor necrosis factor alpha (TNF-alpha), whereas the production of TNF-alpha was not affected with anti-IL-8. Injection of IL-8 did not induce TNF-alpha production and anti-TNF-alpha had no effect on IL-8-induced VP. Injection of homologous TNF-alpha induced IL-8 production and VP, and TNF-alpha-induced delayed VP was blocked with anti-IL-8. These results indicate important roles of IL-8 in LPS-induced delayed VP and that TNF-alpha causes the delayed VP through the production of IL-8.

Animals↗